Papules, Craters and Umbilication: Molluscum Contagiosum

MOJ Tumor Research

Mini Review Open Access Papules, craters and umbilication: molluscum contagiosum Molluscum contagiosum Volume 1 Issue 5 - 2018 (MC) is a cutaneous contamination with a pox virus discovered in 1 2 children. Bateman first scripted the entity in 1817. Individuals with Anubha Bajaj a normal immune function tend to recover spontaneously, though Consultant Histopathology, Panjab University, India the disease can prolong for months. The therapeutic options are numerous including simple observation.1 Efficacious therapies may Correspondence: Anubha Bajaj, Consultant Histopathology, be mechanical, chemical, immune-modulation or antiviral. Panjab University, India, Email [email protected] Received: October 26, 2018 | Published: October 31, 2018 Determinants Molluscum Contagiosum originates from a pox virus of the mollusci pox genus belonging to the pox viridae family. Molluscum yellow, flesh coloured, translucent, pink or red (inflamed).1 The moist contagiosum virus (MCV) is a sizable, brick shaped, double stranded zones or areas of abrasion are implicated especially the extremities DNA virus of 200-3000 nm dimension. The virus genome is covalently ( intertriginous region), trunk and face in the children. The adults coupled at both edges and encodes 182 proteins with 105 direct manifest the lesions in the lower abdomen, upper thighs, pubic analogues with the ortho pox virus (3)Molluscum contagiosum virus area, anus and genital region. Uncommonly the nipples, aerolae, has 4 major subclasses: MCV 1 as a subclass occurs frequently (75- conjunctiva, lips, eyelids, oral mucosa, scalp and soles of the feet are 96%) with MCV 2( 5%), MCV 4(9%) and MCV3(11%). Paediatric incriminated. Numerically the papules are <20 and range from 1-5 patients are generally infected with MCV subclass 1. MCV subclass mm in diameter. The lesions may be asymptomatic but can undergo 2 induces a sexually transmitted disease, prevalent in teenagers and inflammation, accumulation and display a linear pattern with auto- adults. MCV subclass 2 is antecedent to nearly 60% of the viral inoculation. Occasionally, they may be solitary. Miniscule papules disorders co-infected with HIV. Thus molluscum contagiosum when and paediatric patients may not demonstrate a central crater.1 The co-exists with HIV, does not imply a reoccurrence in paediatric rare congenital lesions exhibit a halo about the scalp.3 A pallid, hypo- infections. Usually an individual represents infectivity of a single pigmented halo or a ring (Woronoff ring) abutting the viral papules is viral subclass.3 noted (halo phenomenon). At the site of retrogression, the lesions are oedematous, inflamed and erythematosus.7 “ BOTE” Beginning of the Existence end is a term utilized for the regressing, inflammatory lesions which is Molluscum Contagiosum is prevalent worldwide. However it defined by the variable immune reaction to the viral ingress instead of frequently inhabits tropical and humid climates.1,4 The irrefutable a secondary bacterial contagion, in patients with adequate immunity. reservoir for Molluscum contagiosum is humans MCV infection Lesions in the immune –compromised are extensive, preponderantly is recorded in 1% of the diagnosed dermatological disorders. The >1cm in diameter (giant molluscum contagiosum) and may exhibit paediatric cases such as the pre school/ elementary school children are an anomalous representation and location such as a verrucous or a 1 hypertrophic emergence. The protuberant papules develop rapidly, implicated with 5 % to 11.5% prevalence. MC is infrequent below 1 8 year of age as is congenital MC. Both genders are equally incriminated. disseminate, recur and are resistant to therapy. Poor hygiene, poverty, cramped living conditions predispose to MC. Interpretation Physical touch, autoinoculation and contaminated fomites( clothing, bath sponges, towels and wet skin ) help to disseminate the virus.5 Physical inspection and clinical examination are the mainstay Autoinoculation with a bunch of lesions ensue due to rubbing and of diagnosis. The discrete, smooth, flesh coloured, dome shaped scratching and is a probable mode of transmission in children. The papules with a central umbilicus are characteristic. A magnifying virus is sexually transmitted in adults via tattoos and in swimming lens or a dermatoscope assists in viewing the central umbilicus pools with the lesions elucidating a bathing suit distribution. Vertical which depicts a poly-lobular or four leaf clover- like yellowish white dissemination of the virus from the mother to the foetus via an infected amorphous configuration with tangential reddish, linear or branching birth canal or an ascending infection with premature rupture of blood vessels. These attributes are not visible to the un-aided eye. membranes is described.3 The MCV infection emanates in the first six Molecular techniques such as the Polymerase Chain Reaction (PCR) weeks of life. Immune deficiency (HIV infection) or atopic dermatitis are beneficial in correlating the clinical features and epidemiology of predispose to the viral disease.1,6 5-18% of the patients display a co- the pox virus infection. However, the technology lacks utilization in infection of HIV with MCV. daily practice.9 Clinical phenomenon Excision biopsy Incubation varies from 2-7 weeks and the infection can manifest Excision biopsy is advantageous in problematic lesions with in up to 26 weeks. The classic lesions of MC evolve as discrete, anomalous morphology. Histopathology elucidates the typical firm, smooth, dome- shaped waxy papules with a typical central enormous, eosinophilic, intra-cytoplasmic inclusion bodies visualized umbilicus occluded with oozing, cheesy matter comprised of dead on routine H & E stained sections. The centric corpus is detailed with epithelial cells and virus particles.1The lesions can be pearly white, exudation of pearly, keratinous material. Light microscopy defines a

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dermis notched by the epithelial proliferation. Cellular differentiation within the papule packs the cytoplasm with a granular, eosinophilic expansion which dislocates the nucleus. The signature molluscum bodies are composed of viral fragments identical in size and disposition to poxviruses. The circumferential dermis is profoundly inflamed, configuring as an abscess or a pleomorphic Tcell infiltrate which may resemble a lymphoma /leukaemia proliferation. Metaplastic ossification may be detected. Light microscopy also delineates a lobular, circumscribed lesion with epithelial hyperplasia, prominent keratinisation and a transposed basement membrane. The encompassing stroma ranges from being fibrous, adenomatous and myxomatous. A dense, fine vasculature can be elucidated in the viral lesions on immunohistochemistry (IHC) and CD34 monoclonal Figure 2 Viral particles as intracytoplasmic inclusions. antibodies. Vacuolated, amphophilic cytoplasm with prominent nucleoli are evident. The epithelial hyperplasia and keratinocytes exhibit multiple discrete, ovoid, large, eosinophilic intracytoplasmic inclusion bodies(Henderson-Patterson or Molluscum Bodies) with a condensed nucleus stretched across the cell membrane, thus developing a signet ring appearance. Follicular neo-genesis has been hypothesized as the originator of the pox virus infection by virtue of the foci of circumferential hair bulb differentiation with sporadic sebaceous gland discrimination.10 However zones of minimal /absent hair follicles such as the palm may elucidate the condition, thereby signifying epidermal transformation. The hand held reflectance con- focal microscope is a rapid, non-invasive mechanism which can utilized for the detection of the disorder. Central crater with hypertrophic keratinocytes. Electron microscopy Figure 3 Demonstrates typical brick shaped viral particles within the intra- cytoplasmic inclusion bodies.MCV multiplies in the epidermal stratum spinosum following infection of the epidermis. The keratinocytes hypertrophy and in conjunction with viral replication, display the distinctive intra-cytoplasmic viral inclusion bodies. Innumerable virions are enclosed in the intracellular compartment enclosed within a collagen and lipid rich vesicle. The eosinophilic intra-cytoplasmic inclusions can be demonstrated on H& E stained sections.6 The host cell, when breached on extermination, dispenses the viral particles in order to contaminate fresh epithelium (Figures 1−5).

Figure 4 Pox virus particles as eosinophilic inclusions.

Figure 5 Molluscum of the Cervix with inclusions and inflammation- Cytology Figure 1 Epithelial hyperplasia with a central crater. smear.

Citation: Bajaj A. Papules, craters and umbilication: molluscum contagiosum. MOJ Tumor Res. 2018;1(5):167‒170. DOI: 10.15406/mojtr.2018.01.00037 Copyright: Papules, craters and umbilication: molluscum contagiosum ©2018 Bajaj 169

Ramifications Acantholytic acanthoma: Asymptomatic benign skin tumours with typical acanthosis and acantholysis usually elucidate as keratotic The papules can be hideous and distressing Giant, expansive, papules or nodules on the torso. The elderly are predisposed with external lesions may motivate parental apprehension. Secondary Male: Female proportions at 2:1. bacterial infection (aftermath of irritation induced impetiginisation), irritation, inflammation, conjunctivitis and superficial punctate Epidermoid cyst: is a fluctuant, indolent, firm, dome shaped lesion keratitis are implicated.1,3 Eczematous dermatitis is demonstrated adherent to the skin excluding the subcutaneous tissue. A central core in 10% cases at the perimeter of the lesions. The dermatitis recedes may be visible. 3 spontaneously with the elimination of the viral lesions. Folliculitis, Subepidermal calcified nodule: Commences as a dome shaped, firm, erythema multiforme, erythema annulare centrifugum and infected solitary, yellowish white or erythematous, well circumscribed, papule epidermoid cyst secondary to the pox virus ingress is infrequent. or nodule with a smooth or a verrucous crust generally appearing in Conclusions and substitution the head and neck. Immune-deficiency: Delineates fungal contamination such as Besides the Table 1, alternatives that require distinction are: cryptococcosis, histoplasmosis, penicillosis, aspergillosis and coccidiomycosis in varied organs. Table 1 Inflammatory

Lesion Clinical features Gross examination Gross examination Preferential sites Non inflammatory follicles papules, Inflammatory Papules, Upper Chest, Face, Acne Vulgaris Comedones open/closed comedones Pustules, Nodules. Back. Occurs in Adolescence Rose coloured Macules, Papules, Pustules on crust, new 250-500 lesions. Pruritus Central distribution, Chicken Pox Vesicles, Dew drops on rose petals lesions in 1-2 days, with skin rash. Scarring. trunk Asymptomatic, small, well Peels to punctate black Fingers, dorsum of the Common Yellow/gray/brown, flesh circumscribed, papule, nodule, dots due to thrombosed hands, toes, elbows Warts(Verruca Vulgaris) coloured. hyperkeratotic/verrucous surface capillaries knees, face.

Papular Pink to red brown Symmetrical and typical Acute onset, multiple, monomorphic, Lesions on the trunk acrodermatitis(Gianotti papules or papulo- distribution on the extensor flat topped lesions. are mild –Crosti Syndrome) vesicles surface of extremities. Small<3mm, white, benign, dome Congenital milia favour Milia Primary milia of children Prefer eyelids. shaped, superficial keratinous cysts the nose Papules 1-3 mm in Localized common & Small, soft to firm, skin coloured or Solitary/multiple, localized or Syringoma diameter, asymptomatic periorbital. Generalized yellowish papules generalized and symmetric chest, neck forearms.

Asymptomatic, isolated or grouped Thick, chalky, cheesy material Vermilion border of the Fordyce Spots minute, discrete, creamy yellow Bilateral and Symmetrical expressed lips, Penis, scrota, labia, papules Extensor surface Abrupt onset, yellow orange papules, Eruptive Xanthoma, Hyperlipidemia of extremities and crops buttocks Intense pruritus, grouped or Hypersensitivity to insect 3-10 years, summer or Papular Urticaria Central crater discriminative urticarial papules bites and stings late spring

Asymptomatic Multiple, Few mm to centimetres, Oily or creamy content. Chest, neck, axilla, smooth round, movable, soft, Steatocystoma Multiplex slow growing. No central Overlying epidermis is proximal extremities yellow(superficial) or skin coloured umbilicus normal and groin. (deeper)papules and nodules

Folliculitis Small, discrete pustules, erythematous base, Around hair follicles Soft, flesh coloured, flat, ragged Condylomata Acuminata Warty Papules, Cauliflower growths, velvety plaques Peri-anal area papules Abrupt onset Discrete, flesh, pink, tan Lichen Striatus 1-3mm, continuous or interrupted linear bands which may curve erythematous flat topped papules

Flexor aspect of the Pruritus, purple, planar or polygonal Lacy, reticular white lines Symmetric, Koebner’s wrist and ankles Dorsa Lichen Planus plaque or papules : Wickham’s Striae phenomenon of the hand, trunk, shins, glans penis

Therapeutics Outcome Generic preventions: Communal use of bed linen, towel, sponges, Majority of the cases recover automatically without progression in bath tubs, swimming pools, contact sports should be circumvented. 6.5 to 13 months but may persevere for decades. Abstinence from scratching, rubbing, picking and squeezing the lesions with finger nails is necessary as the central plugs are fraught Acknowledgements with the viral particles inducing dispersal. None. Simple observation: Spontaneous recovery is anticipated particularly with temperate disease and in fragile regions such as the face & groin. Conflict of interest Progressive intervention: Molluscum Contagiosum is a self limiting The author declares that there is no conflict of interest. condition. Active intervention is required for cosmetic purposes and to relieve irritation, itching, transmission and inoculation.1,4,5 References 1. Leung AK. Molluscum Contagiosum. Current Paediatric Review. Mechanical measures: Cryo-therapy with liquid nitrogen, curettage 2012;8(4):346‒9. and pulsed dye laser therapy are efficacious though painful and morbid.1 Topical anaesthesia with eutectic mixtures of local anaesthetics 2. Bateman F. Molluscum Contagiosum. In: Shelley WB, Crissy T, Editors. can also be employed Adverse reaction to Liquid nitrogen are pain, Classic in Dermatology: Spring field Illinois. Charles C Thomas. 1953. 20 p. erythema, vesicle formation and de-pigmentation Currettage may result in pain, minor bleeding and scarring. Pulse dye laser therapy is 3. Nguyen HP. Treatment of Molluscum Contagiosum in adult, paediatric and a competent and safe method appropriate for refractory lesions. immune- deficient population.J Catan Med Surg. 2014;18(5):299‒306. Chemical composites: Substitutes such as Cantharidrin, KOH, 4. Van Der Wouden JC. Interventions for cutaneous Molluscum Contagiosum. podophyllotoxin, benzoyl peroxide, tretinoin, trichloracetic acid, Cochrane Database Systematic Review. 2009:4;CD004767. lactic acid, glycolic acid, salicylic acid can be anointed but a local 5. Jones S. Treatment of Molluscum Contagiosum and Herpes Simplex inflammation may ensue. Cantharidrin may incite uneasiness, Virus Cutaneous Infection. Cutis. 2007;79(Suppl 4):11‒7. pain, blister formation and a post inflammatory de-pigmentation. 6. Rush J. New discoveries and guidelines regarding management of Application of cantharidrin at intertriginous regions should be bacterial soft tissue infections, Molluscum Contagiosum and Warts. Curr restricted as it escalates the inflammation. Opin Paediatr. 2016;28(2):250‒7. Immune modulatory: Mthods such as Topical Imiquimod, Interferon 7. Berger EM. Experience with Molluscum Contagiosum and associated alpha, Cimetidine dispense cytokines. Alpha interferon, a glycoprotein inflammatory reactions in paediatric dermatology practice: The bump that cytokine, annihilates the virus particles so the viral infection rashes. Arch Dermatol. 2012;148(11):1257‒64. retrogresses. It is utilized in immune- deficient patients elucidating 8. Erickson C. Efficacy of Intravenous cidofovir in the treatment of giant severe, recalcitrant lesions. It can be administered as subcutaneous or molluscum contagiosum in patients with Human Immune-Deficiency. within the lesion. Arch Dermatol. 2011;147(6):652‒4. Antiviral therapy: With Topical or Intravenous Cidofir can be 9. Alexander K Leung. Molluscum Contagiosum: An Update. Recent employed in a severe, refractory disease. Topical application is patients on inflammation and allergy drug discovery. 2017;11(1);22‒31. adopted as the intravenous mode is nephrotoxic. Adverse reactions 10. Reed RJ, Parkinson RP. The histogenesis of Molluscum Contagiosum. Am such as irritation, erosion, post inflammatory alterations and superficial J Surg Pathol. 1977;1(2):161‒166. scarring at the site of administration can be delineated. Cochrane systematic review provides inadequate evidence with respect to the efficacy or excellence of a specific treatment modality.4 The preferential therapy varies with the physician’s comfort level, selective treatments, patients’ age, severity and site of lesions, the inclination of the patients besides comprehensive effectiveness, disbursement, adverse reactions, manageable and possible administration. Anti-viral drugs are recommended for treating the refractory lesions.

Citation: Bajaj A. Papules, craters and umbilication: molluscum contagiosum. MOJ Tumor Res. 2018;1(5):167‒170. DOI: 10.15406/mojtr.2018.01.00037